Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components

Chan Yen Ou; Vivian Y. Poon; Celine I. Maeder; Shigeki Watanabe; Emily K. Lehrman; Amy K.Y. Fu; Mikyoung Park; Wing Yu Fu; Erik M. Jorgensen; Nancy Y. Ip; Kang Shen

doi:10.1016/j.cell.2010.04.011

Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components

Chan Yen Ou, Vivian Y. Poon, Celine I. Maeder, Shigeki Watanabe, Emily K. Lehrman, Amy K.Y. Fu, Mikyoung Park, Wing Yu Fu, Erik M. Jorgensen, Nancy Y. Ip, Kang Shen

Research output: Contribution to journal › Article › peer-review

115 Scopus citations

Abstract

Polarized trafficking of synaptic proteins to axons and dendrites is crucial to neuronal function. Through forward genetic analysis in C. elegans, we identified a cyclin (CYY-1) and a cyclin-dependent Pctaire kinase (PCT-1) necessary for targeting presynaptic components to the axon. Another cyclin-dependent kinase, CDK-5, and its activator p35, act in parallel to and partially redundantly with the CYY-1/PCT-1 pathway. Synaptic vesicles and active zone proteins mostly mislocalize to dendrites in animals defective for both PCT-1 and CDK-5 pathways. Unlike the kinesin-3 motor, unc-104/Kif1a mutant, cyy-1 cdk-5 double mutants have no reduction in anterogradely moving synaptic vesicle precursors (SVPs) as observed by dynamic imaging. Instead, the number of retrogradely moving SVPs is dramatically increased. Furthermore, this mislocalization defect is suppressed by disrupting the retrograde motor, the cytoplasmic dynein complex. Thus, PCT-1 and CDK-5 pathways direct polarized trafficking of presynaptic components by inhibiting dynein-mediated retrograde transport and setting the balance between anterograde and retrograde motors.

Original language	English (US)
Pages (from-to)	846-858
Number of pages	13
Journal	Cell
Volume	141
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2010.04.011
State	Published - May 2010
Externally published	Yes

Keywords

Molneuro

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2010.04.011

Cite this

@article{2438a1c1ebfd480ca752d88003092cde,

title = "Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components",

abstract = "Polarized trafficking of synaptic proteins to axons and dendrites is crucial to neuronal function. Through forward genetic analysis in C. elegans, we identified a cyclin (CYY-1) and a cyclin-dependent Pctaire kinase (PCT-1) necessary for targeting presynaptic components to the axon. Another cyclin-dependent kinase, CDK-5, and its activator p35, act in parallel to and partially redundantly with the CYY-1/PCT-1 pathway. Synaptic vesicles and active zone proteins mostly mislocalize to dendrites in animals defective for both PCT-1 and CDK-5 pathways. Unlike the kinesin-3 motor, unc-104/Kif1a mutant, cyy-1 cdk-5 double mutants have no reduction in anterogradely moving synaptic vesicle precursors (SVPs) as observed by dynamic imaging. Instead, the number of retrogradely moving SVPs is dramatically increased. Furthermore, this mislocalization defect is suppressed by disrupting the retrograde motor, the cytoplasmic dynein complex. Thus, PCT-1 and CDK-5 pathways direct polarized trafficking of presynaptic components by inhibiting dynein-mediated retrograde transport and setting the balance between anterograde and retrograde motors.",

keywords = "Molneuro",

author = "Ou, {Chan Yen} and Poon, {Vivian Y.} and Maeder, {Celine I.} and Shigeki Watanabe and Lehrman, {Emily K.} and Fu, {Amy K.Y.} and Mikyoung Park and Fu, {Wing Yu} and Jorgensen, {Erik M.} and Ip, {Nancy Y.} and Kang Shen",

note = "Funding Information: This work was supported by the Human Frontier Science Foundation, the W.M. Keck Foundation, and the Howard Hughes Medical Institute. We thank the International C. elegans Gene Knockout Consortium, the National Bioresource Project-Japan, and the Nonet lab for strains. We also thank Y. Wu, M. Margeta, C. Gao, and Y. Fu for technical assistance, and C. Bargmann, L.H. Tsai, and members of the Shen lab for thoughtful comments on the manuscript. ",

year = "2010",

month = may,

doi = "10.1016/j.cell.2010.04.011",

language = "English (US)",

volume = "141",

pages = "846--858",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

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TY - JOUR

T1 - Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components

AU - Ou, Chan Yen

AU - Poon, Vivian Y.

AU - Maeder, Celine I.

AU - Watanabe, Shigeki

AU - Lehrman, Emily K.

AU - Fu, Amy K.Y.

AU - Park, Mikyoung

AU - Fu, Wing Yu

AU - Jorgensen, Erik M.

AU - Ip, Nancy Y.

AU - Shen, Kang

N1 - Funding Information: This work was supported by the Human Frontier Science Foundation, the W.M. Keck Foundation, and the Howard Hughes Medical Institute. We thank the International C. elegans Gene Knockout Consortium, the National Bioresource Project-Japan, and the Nonet lab for strains. We also thank Y. Wu, M. Margeta, C. Gao, and Y. Fu for technical assistance, and C. Bargmann, L.H. Tsai, and members of the Shen lab for thoughtful comments on the manuscript.

PY - 2010/5

Y1 - 2010/5

N2 - Polarized trafficking of synaptic proteins to axons and dendrites is crucial to neuronal function. Through forward genetic analysis in C. elegans, we identified a cyclin (CYY-1) and a cyclin-dependent Pctaire kinase (PCT-1) necessary for targeting presynaptic components to the axon. Another cyclin-dependent kinase, CDK-5, and its activator p35, act in parallel to and partially redundantly with the CYY-1/PCT-1 pathway. Synaptic vesicles and active zone proteins mostly mislocalize to dendrites in animals defective for both PCT-1 and CDK-5 pathways. Unlike the kinesin-3 motor, unc-104/Kif1a mutant, cyy-1 cdk-5 double mutants have no reduction in anterogradely moving synaptic vesicle precursors (SVPs) as observed by dynamic imaging. Instead, the number of retrogradely moving SVPs is dramatically increased. Furthermore, this mislocalization defect is suppressed by disrupting the retrograde motor, the cytoplasmic dynein complex. Thus, PCT-1 and CDK-5 pathways direct polarized trafficking of presynaptic components by inhibiting dynein-mediated retrograde transport and setting the balance between anterograde and retrograde motors.

AB - Polarized trafficking of synaptic proteins to axons and dendrites is crucial to neuronal function. Through forward genetic analysis in C. elegans, we identified a cyclin (CYY-1) and a cyclin-dependent Pctaire kinase (PCT-1) necessary for targeting presynaptic components to the axon. Another cyclin-dependent kinase, CDK-5, and its activator p35, act in parallel to and partially redundantly with the CYY-1/PCT-1 pathway. Synaptic vesicles and active zone proteins mostly mislocalize to dendrites in animals defective for both PCT-1 and CDK-5 pathways. Unlike the kinesin-3 motor, unc-104/Kif1a mutant, cyy-1 cdk-5 double mutants have no reduction in anterogradely moving synaptic vesicle precursors (SVPs) as observed by dynamic imaging. Instead, the number of retrogradely moving SVPs is dramatically increased. Furthermore, this mislocalization defect is suppressed by disrupting the retrograde motor, the cytoplasmic dynein complex. Thus, PCT-1 and CDK-5 pathways direct polarized trafficking of presynaptic components by inhibiting dynein-mediated retrograde transport and setting the balance between anterograde and retrograde motors.

KW - Molneuro

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U2 - 10.1016/j.cell.2010.04.011

DO - 10.1016/j.cell.2010.04.011

M3 - Article

C2 - 20510931

AN - SCOPUS:77953266051

SN - 0092-8674

VL - 141

SP - 846

EP - 858

JO - Cell

JF - Cell

IS - 5

ER -

Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components

Abstract

Keywords

ASJC Scopus subject areas

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